PROJECT SUMMARY Iron deficiency is the most common micronutrient deficiency globally and is a leading risk factor for anemia, poor cognitive development, and impaired immune function among children. However, iron also plays an essential role in the life cycle of HIV and opportunistic infections, calling into question the relative safety and benefits of iron supplementation among HIV-infected populations. Epidemiologic studies of HIV-infected adults suggest harmful effects of elevated iron status, protective effects of iron deficiency, and uncertain effects of iron supplementation. The role of iron in pediatric HIV infection and disease is less certain due to the higher prevalence of iron deficiency among children as well as differences between adult and pediatric HIV transmission, clinical presentation, and treatment approach. This study will use data from two large cohorts of HIV-infected and HIV-exposed children in Tanzania to explore the following specific aims: (1) the association of baseline and time-varying anemia, iron deficiency anemia, and iron supplementation with the rate of mortality among HIV-infected children; (2) the incidence, timing, and severity of mortality risk factors in relation to iron status; and (3) whether maternal iron status and iron supplementation are associated with mother-to-child transmission of HIV as well as morbidity and mortality due to other infections. Data from two sources will be leveraged: an observational cohort study of HIV-infected children (n=5188) in the Dar es Salaam region of Tanzania and from a randomized controlled trial of Tanzanian children (n=2387) born to HIV-infected mothers and followed until 18 months of age. Generalized linear mixed models and marginal structural Cox models will be used. The results will inform the potential for iron homeostasis as a therapeutic target for HIV, and whether iron supplementation poses risks to HIV-infected children.